The goal of this proposal is to develop a new treatment for strabismus, a visual disorder affecting 3-4% of the population, using a novel technology that we have recently formulated. This involves specific targeting and elimination of cholinergic motor neurons that innervate the extra-ocular muscles by injection of an antivesicular acetylcholine transporter-saporin (anti-VAChT-saporin). This approach offers some important advantages compared to corrective surgery (the most commonly employed procedure) as well as injections of botulinum toxin A (trade name Botox). Specific Aim 1 is to manufacture a new immunotoxin (termed IX-146) that will specifically target cholinergic neurons in the primate extraocular nuclei. In Specific Aim 2 we will assess the feasibility of using IX-146 for the treatment of strabismus. After injection of IX-146 into the lateral rectus muscle the resulting degree of strabismus will be measured using state of the art eye tracking methodologies. In Phase II of the project we will assess the efficacy of IX-146 treatment for strabismus. The use of IX-146 could be extended in the future to a wider variety of ophthalmologic, neurologic, and neuromuscular disorders, including blepharospasm as well as other types of dystonias.